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靶向血管内皮生长因子受体2的超声造影对裸鼠肝癌皮下移植瘤模型中抗血管生成治疗反应的无创监测价值

Value of ultrasound-targeted vascular endothelial growth factor receptor-2 in non-invasive monitoring of anti-angiogenic response in nude mice with subcutaneous xenograft model

摘要:

目的:探讨靶向血管内皮生长因子受体2(VEGFR-2)的超声造影对裸鼠肝癌皮下移植瘤模型中抗血管生成治疗反应的无创监测价值。方法:将16只裸鼠随机分为对照组和贝伐单抗治疗组(治疗组),建立皮下移植瘤模型,建模2周后,治疗组小鼠给予0.2 mg贝伐单抗瘤内注射治疗,对照组给予等量生理盐水,每周注射3次,连续治疗2周。采用生物素-亲和素法制备靶向VEGFR-2的超声微泡造影剂,分别于治疗前、治疗7 d和治疗14 d行超声检查,绘制时间-强度曲线(TIC),定量分析各参数随治疗时间变化的差异。采用免疫组化法检测各组小鼠肿瘤组织中CD31的表达。结果:治疗14 d后,治疗组和对照组裸鼠肿瘤组织的体积分别为(0.247±0.019)mm 3和(0.307±0.031)mm 3,差异有统计学意义( P<0.01)。治疗7 d后,治疗组TIC曲线上升斜率(K 1)、达峰时间(TTP)和峰值强度(PI)分别为3.77±0.62、(3.82±0.21) s和(24.35±3.34) dB,与对照组[分别为2.93±0.31、(4.47±0.50) s和(30.10±2.35) dB]比较,差异均有统计学意义(均 P<0.05)。免疫组化结果显示,小鼠超声造影PI与微血管密度呈正相关( r2=0.898, P=0.017)。 结论:靶向VEGFR-2超声造影评价贝伐单抗抗肿瘤血管生成的治疗效果与TIC指标中K 1、TTP和PI等参数的差异变化有关,靶向VEGFR-2的超声造影对无创监测裸鼠肝癌皮下移植瘤模型具有重要价值。

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abstracts:

Objective:To investigate the value of contrast-enhanced ultrasound targeting vascular endothelial growth factor receptor-2 (VEGFR-2) in non-invasive monitoring of anti-angiogenesis response in subcutaneous transplantation tumor model of hepatocellular carcinoma in nude mice.Methods:Sixteen nude mice were randomly divided into control group and bevacizumab treatment group (treatment group). Two weeks later, the model of subcutaneous transplanted tumor was established. The mice in the treatment group were intratumorally injected with 0.2 mg bevacizumab, while the control group was given the same amount of saline, three times a week for 2 weeks. Ultrasound microbubbles targeting VEGFR-2 were prepared by biotin avidin method. Ultrasound examinations were performed before treatment, 7 days and 14 days after treatment, and the time intensity curve (TIC) was drawn to quantitatively analyze the differences of parameters with treatment time. The expression of CD31 in tumor tissues was detected by immunohistochemistry.Results:After 14 days of treatment, the volume of tumor tissue in the treatment group and the control group were (0.247±0.019) mm 3 and (0.307±0.031) mm 3, respectively, the difference was statistically significant ( P<0.01). After 7 days of treatment, the rise slope (K 1), time to peak (TTP) and peak intensity (PI) of TIC curve in the treatment group were 3.77±0.62, (3.82±0.21) s and (24.35±3.34) dB, respectively, which were significantly different from 2.93±0.31, (4.47±0.50) s and (30.10±2.35) dB in the control group, respectively ( P<0.05). Immunohistochemistry showed that the PI of contrast enhanced ultrasound was positively correlated with microvessel density ( r2=0.898, P=0.017). Conclusions:The therapeutic effect of bevacizumab on tumor angiogenesis evaluated by contrast-enhanced ultrasound targeting VEGFR-2 is related to the differences of parameters such as K 1, TTP and PI of TIC index. Contrast enhanced ultrasound targeting VEGFR-2 is of great value in non-invasive monitoring of subcutaneous transplanted tumor model of hepatocellular carcinoma in nude mice.

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作者: 汪玲 [1] 陆英慧 [1] 王天佑 [2]
期刊: 《中华肿瘤杂志》2020年42卷10期 856-860页 MEDLINEISTICPKUCSCDCABP
栏目名称: 基础研究
DOI: 10.3760/cma.j.cn112152-20191230-00854
发布时间: 2020-11-16
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